P796: HOSPITALIZATION IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A RETROSPECTIVE ANALYSIS OF OBSERVATIONAL STUDY DATA FROM THE UNITED STATES
Authors: Jamile Shammo, Julia Kim, Mahnouch Georget, Thirupathi Pattipaka, Jilles M Fermont
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematological disorder characterized by intravascular hemolysis (IVH), thrombophilia and bone marrow failure (BMF). PNH is clinically heterogeneous, and hospitalization and regular transfusions may be needed. Treatment with currently approved C5 inhibitors (C5i), eculizumab and ravulizumab, have shown efficacy in IVH control and reduction in thrombosis risk. Despite C5i therapy, many patients (pts) continue to be anemic with a subset remaining transfusion dependent. Aims: To better understand the burden of PNH, obtain insights into clinical outcomes and further characterize residual anemia after C5i, using health record data. Methods: In this retrospective observational study we analyzed 1138 pts aged ≥18 years diagnosed with PNH in the TriNetX network who had ≥180 days of post-diagnosis follow-up data. PNH-related hospitalization was defined by specific International Classification of Diseases (ICD) codes. Treatment response was defined according to EBMT criteria and assessed over 180 days after C5i initiation. Signs of anemia were identified from hemoglobin (Hb) level, ICD of iron deficiency or iron infusion, and assessed at baseline and ≥180 days after C5i initiation. Hazard ratios (HR) [95% confidence interval (CI)] associated with Hb levels for the first hospitalization were estimated using age- and sex-adjusted Cox regression. Rate ratios (RR) were estimated using age- and sex-adjusted negative binomial models for transfusion as recurrent events and length of hospital stay. Results: Overall, 59% of pts were female and the median (interquartile range [IQR]) age was 56 (39–68) years. Most pts had PNH with BMF (67%) followed by classic PNH (20%), 14% had PNH subtype unclassified. During the 12 months prior to PNH diagnosis (baseline), 588 (52%) pts experienced ≥1 hospitalization with infections (28%), anemia (27%), dyspnea (26%), abdominal pain (25%) and thrombosis (24%) as leading causes. Median (IQR) Hb level at baseline was 11 (9–13) g/dL and 52% of pts had evidence of anemia. During a median follow-up of 2.6 years, 612 (54%) pts experienced ≥1 hospitalization with a median (IQR) 3 (1–8) days stay for the first hospitalization, and 242 (21%) pts required ≥1 transfusion. Lower Hb at baseline was associated with a higher rate of hospitalization (HR=1.10 [1.07–1.14] per 1 g/dL decrease), longer hospital stay (RR=1.07 [1.02–1.11] per 1 g/dL decrease) and higher transfusion rate (RR=1.88 [1.68–2.11]). Anemia was associated with higher rates of hospitalization (HR=2.18 [1.85–2.58]) and transfusion (RR=6.76 [4.02–11.37]). In total, 160 (14%) pts received C5i, of whom 114 (71%) remained anemic 1 year after C5i initiation. In addition, 57 (36%) C5i-treated pts still required transfusions (rate=0.97 [0.90–1.05]) during follow-up. Anemia (42%), infections (41%), abdominal pain (27%), dyspnea (24%) and thrombosis (23%) remained leading causes of hospitalization (rate=0.55 [0.50–0.62]). Interestingly, during the course of C5i therapy, 93 (58%) pts progressed to BMF (23 had BMF at baseline), 29% had signs of IVH, 34% EVH and 29% breakthrough hemolysis. Summary/Conclusion: Findings demonstrate substantial disease burden and healthcare resource utilization for PNH pts including those treated with C5i, albeit a small subset of this cohort. Despite well-established efficacy of C5i, we found that residual anemia and hemolysis still affect many treated PNH pts. Our data have limited statistical power and longer follow-up is needed. However, these findings support the need to address disease burden and improve disease management. Keywords: Paroxysmal nocturnal hemoglobinuria (PNH), Anemia, Real world data